This is an application for continuing support for a program focused on the regulatory mechanisms of enterostatin. The peptide enterostatin is a product of a prepeptide called procolipase, which was originally identified in the gut in connection with fat absorption. The previous support for this project has allowed progress in which the investigator has provided evidence for both peripheral and central sites of action for enterostatin. The presumption currently is that the central enterostatin action sites are separate and may be responding to a separate source of enterostatin. Given the current state of knowledge in this area the investigator identifies the following aims for this proposal. First they seek to identify the enterostatin receptor by an expression cloning technique. Second they will characterize the enterostatin receptor and its regulation by dietary fat and by hormones. Third they will investigate how signaling pathways activated by fatty acids in the mouth or gut interact with enterostatin responsive pathways to regulate fat intake. Fourth they will identify the neuropathways responsive to enterostatin by immunohistochemistry and tract tracing techniques. Finally these pathway responsiveness to dietary fat will be evaluated.